Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma

Chun Te Ho, Hung Sheng Shang, Jin Biou Chang, Jun Jen Liu, Tsan Zon Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Patients with hepatocellular carcinoma (HCC) are prone to folate deficiency (FD). Here we showed that, in cell line-specific manner, FD caused resistance to FD-induced oxidative stress and multi-drug resistance (MDR). This resistance was due to upregulation of glucose-regulated protein 78 (GRP78) and Survivin. Using siRNA and Epigallocatechin gallate (EGCG), we found that GRP78 and Survivin cooperatively conferred MDR by decreasing FD-induced ROS generation. Our data showed that FD increases GRP78 and Survivin, which serve as ROS inhibitors, causing MDR in HCC. We suggest that folate supplementation may enhance the efficacy of chemotherapy.

Original languageEnglish
Pages (from-to)26104-26118
Number of pages15
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 2015

Fingerprint

Folic Acid
Drug Resistance
Oxidation-Reduction
Hepatocellular Carcinoma
Multiple Drug Resistance
Small Interfering RNA
Oxidative Stress
Up-Regulation
Drug Therapy
Cell Line
glucose-regulated proteins

Keywords

  • chemotherapy
  • Folate
  • GRP78
  • hepatoma
  • multi-drug resistance

ASJC Scopus subject areas

  • Oncology

Cite this

Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma. / Ho, Chun Te; Shang, Hung Sheng; Chang, Jin Biou; Liu, Jun Jen; Liu, Tsan Zon.

In: Oncotarget, Vol. 6, No. 28, 2015, p. 26104-26118.

Research output: Contribution to journalArticle

Ho, Chun Te ; Shang, Hung Sheng ; Chang, Jin Biou ; Liu, Jun Jen ; Liu, Tsan Zon. / Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma. In: Oncotarget. 2015 ; Vol. 6, No. 28. pp. 26104-26118.
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